阿帕替尼联合紫杉醇二线治疗晚期食管癌的临床研究

Clinical study of apatinib combined with paclitaxel in second-line treatment of advanced esophageal cancer

目的研究阿帕替尼联合紫杉醇二线治疗晚期食管癌患者的疗效、不良反应及血清中血管内皮生长因子(vascular endothelial growth factor,VEGF)的变化。方法选取56例无法手术、经一线化疗方案治疗后复发或转移的晚期食管癌患者,根据随机数字表法分为试验组和对照组各28例。试验组经阿帕替尼(500 mg/次,餐后30 min口服)联合。紫杉醇注射液(200 mg/m^2,第1天静脉滴注)治疗;对照组单药紫杉醇化疗(200 mg/m^2,第1天静脉滴注)。两组均21 d为1个周期,4个周期后评估疗效、不良反应及血清VEGF水平。结果试验组因难治性高血压退出1例;对照组因个人原因退出3例。试验组和对照组客观缓解率分别为40.7%(11/27)和16.0%(4/25),疾病控制率分别为81.5%(22/27)和56.0%(14/25)。两组客观缓解率比较,差异具有统计学意义(P<0.05)。试验组治疗前VEGF水平较治疗后降低[(36.19±4.50)ng/mL vs(21.21±2.83)ng/mL,P<0.05]。试验组常见阿帕替尼相关不良反应为高血压(21.4%)、胃肠道反应(10.7%)和白细胞减少(42.9%)等,基本为Ⅰ~Ⅱ级不良反应。两组不良反应发生率比较,差异无统计学意义(P>0.05)。结论阿帕替尼联合紫杉醇二线治疗晚期食管癌患者临床疗效可,不良反应能够耐受,治疗后VEGF水平较治疗前降低。

Objective To study the efficacy,adverse reactions and changes of serum vascular endothelial growth factor(VEGF)in patients with advanced esophageal cancer treated with apatinib combined with paclitaxel.Methods Fifty-six patients with advanced esophageal cancer who could not have surgery and had recurrence or metastasis after treatment with first-line chemotherapy were randomly assigned into the experimental group and control group by a random number table.Twenty-eight patients in the experimental group were treated with apatinib combined with paclitaxel,apatinib 500 mg,orally 30 min after a meal,paclitaxel injection 200 mg/m^2,intravenous drip on the first day,21 d as a cycle.Twenty-eight patients in the control group were treated with single-agent paclitaxel,paclitaxel injection 200 mg/m^2,intravenous drip on the first day,21 d as a cycle.After 4 cycles,the efficacy,adverse reactions,and serum VEGF levels were evaluated between the two groups.Results One of the 28 patients in the experimental group withdrew from the study due to refractory hypertension,and 3 of the 28 patients in the control group withdrew from the study due to personal reasons.The objective response rate of the experimental group and the control group were 40.7%(11/27)and 16.0%(4/25),and the disease control rates were 81.5%(22/27)and 56.0%(14/25).There were statistically significant differences between the two groups(P<0.05).The VEGF level in the experimental group before treatment was lower than that after treatment[(36.19±4.50)ng/mL vs(21.21±2.83)ng/mL,P<0.05].The common apatinib-related adverse reactions in the experimental group were hypertension(21.4%),gastrointestinal reactions(10.7%),and leukopenia(42.9%),which were basically grade Ⅰ~Ⅱ adverse reactions.There was no significant difference in the incidence of adverse reactions between the two groups(P>0.05).Conclusions Apatinib combined with paclitaxel second-line treatment of patients with advanced esophageal cancer is effective.The adverse reactions can be tolerated.The level of VEGF after treatment is significantly lower than that before treatment.